Navigation Links
Excess liver gene protects against high-fat diet

A gene that senses fat in the liver can modulate the consequences of eating a high-fat, Western diet, new research published in the May issue of Cell Metabolism reveals.

Mice with an excess of liver X receptor (LXRa), when fed a diet high in fat, remained free from the high cholesterol and blood vessel plaques exhibited by animals with the normal complement of receptors. Remarkably, in mice fed a normal, balanced diet, the excess receptors worsened blood lipid levels, the researchers reported.

The findings suggest that natural variation among individuals in the quantity of the liver receptors might lead to differences among them in their susceptibility to high cholesterol and heart disease in a manner dependent on diet. Furthermore, drugs that modulate LXRa activity may have potential as therapies for lipid disorders and atherosclerosis, the group said.

"The high-cholesterol, high-fat Western diet has abetted an epidemic of atherosclerotic cardiovascular disease, making it the leading cause of death in industrialized nations," said study senior author Mitchell Lazar, of the University of Pennsylvania School of Medicine. "Yet we know that some people are more susceptible than others to obesity and other problems of excess, suggesting that the interplay between genes and diet is important.

"Now we have a vivid example of a specific genetic alteration with opposite effects in different nutritional environments."

The researchers examined lipid metabolism and atherosclerosis in mice with an approximately 3-fold increase in the concentration of LXRa receptors in their livers. The mice also lacked a second gene that made them particularly prone to cardiovascular disease.

When fed normal mouse chow, mice with a greater than average number of the receptors exhibited a rise in blood cholesterol and triglyceride levels. In contrast, altered mice fed a high-fat, Western diet showed improvements in blood lipid levels and protection from atherosclerosis.

Further experimentation revealed that the increase in LXRa differentially regulated the expression of other important metabolic genes.

"Liver X receptors had emerged as key regulators of cholesterol and lipid metabolism," said Lazar. "The current study elucidates a previously unrecognized role for these liver receptors in the links between diet, serum lipids, and atherosclerosis."

Selective modulation of the LXR target genes in liver may therefore ameliorate high lipid levels and cardiovascular disease, the researchers said.

The researchers include Michael Lehrke, Corinna Lebherz, Segan Millington, Hong-Ping Guan, John Millar, Daniel J. Rader, James M. Wilson, and Mitchell A. Lazar of the University of Pennsylvania School of Medicine. This work was supported by NIH grants, the Penn Diabetes and Endocrinology Research Center, and a Bristol Myers Squibb Freedom to Discover Award in Metabolic Research. M.L. was supported by a Deutsche Forschungsgemeinschaft fellowship.

Lehrke, M., Lebherz, C, Millington, S., Guan, H.-P., Millar, J., Rader, D.J., Wilson, J.M., and Lazar, M.A. (2005). Diet-dependent cardiovascular lipid metabolism controlled by hepatic LXRalpha. Cell Metab. 1, 297-308.


'"/>

Source:Cell Press


Related biology news :

1. Too much of a good thing? Excess nutrients or water limit biodiversity
2. Scientists ID molecular switch in liver that triggers harmful effects of saturated and trans fats
3. New methods of gene delivery using lasers
4. UNC launches study of liver injury caused by drugs
5. Gene therapy cures inherited liver disease in rats
6. Mouse with designer liver has enhanced glucose tolerance, insulin response
7. Recombinant DNA technology may enable oral, rather than injectable, delivery of protein drugs
8. Self-assembled DNA buckyballs for drug delivery
9. Insulin pulses keep the liver lean
10. New research could help us deliver genes for new bone formation
11. “Hitchhiking?Viruses as Cancer Drug Delivery System
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/26/2017)...  Securus Technologies, a leading provider of civil ... investigation, corrections and monitoring, announces the appointment of ... "Too often, too many offenders return to jail ... trying to tackle this ongoing problem and improve ... members. While significant steps are underway, Securus continues to ...
(Date:2/21/2017)... PORTLAND, Ore. , Feb. 22, 2017 /PRNewswire/ ... of Companies (Avamere Health Services, Infinity Rehab, Signature Hospice, ... study that will apply the power of IBM cognitive ... and health centers. By analyzing data streaming from sensors ... into physical and environmental conditions, and obtain deeper learnings ...
(Date:2/14/2017)... WINSTON-SALEM, N.C. , Feb. 14, 2017  Wake ... FRY-shlog), M.D., as its new chief executive officer (CEO). ... succeeds CEO John D. McConnell , M.D., who ... new position at the Medical Center, after leading it ... oversee the full scope of Wake Forest Baptist,s academic ...
Breaking Biology News(10 mins):
(Date:3/22/2017)...  Ascendis Pharma A/S (Nasdaq: ASND), a biopharmaceutical ... address significant unmet medical needs in rare diseases, ... ended December 31, 2016. "2016 ... we broadened our pipeline and pursued our vision ... with an initial focus on endocrinology," said ...
(Date:3/22/2017)... New York , March 22, 2017 ... is largely fragmented, states a research report by Transparency ... S.A., Pfizer Inc., Amgen Inc., and AbbVie Inc., accounted ... in 2015. The prominent players in this market are ... expand their product portfolio, which is likely to lead ...
(Date:3/22/2017)... ... March 21, 2017 , ... Premier executive recruitment firm, Slone Partners, is proud ... Hunt Scanlon Media. , Hunt Scanlon Media is one of the most ... news source in the human capital sector. , “It is a great honor for ...
(Date:3/22/2017)... ... March 21, 2017 , ... The Conference Forum has announced the ... be held on May 10-11, 2017, at the Colonnade Hotel in Boston, MA. The ... Medical Officer peer-to-peer learning, benchmarking and support. , “The Chief Medical Officer faces a ...
Breaking Biology Technology: